Pulse Pressure, Endothelium Function, and Arterial Stiffness in Spontaneously Hypertensive Rats

Abstract

Abstract-In rats, removal of the carotid arterial or abdominal aortic endothelium results in an acute increase of diameter and compliance. In humans, acute local administration of a specific NO synthase inhibitor increases radial artery compliance but not the diameter. The purpose of this review is to determine whether in spontaneously hypertensive rats (SHR), a cause-and-effect relationship may be observed between endothelial function and arterial stiffness with possible consequences on pulse pressure (PP) control. The study is based on a comparative time-dependent analysis of the following in young and old SHR: aortic blood pressure measurements and reactivity, ultrasonographic arterial stiffness assessment, aortic histomorphometry and staining, and molecular biology with evaluation of endothelium function. In young SHR, aortic mean blood pressure and PP increase proportionally, whereas isobaric arterial stiffness is unchanged or poorly modified. The endothelial NO response to norepinephrine is normal or upregulated as a response to predominant vasoconstrictive influences. In contrast, in old SHR, PP and mean blood pressure change disproportionately with age, together with an enhanced isobaric arterial stiffness. The endothelial NO response to norepinephrine is abolished, in association with endothelium-dependent heightened norepinephrine reactivity and enhanced accumulation of vessel extracellular matrix. In this latter case, exogenous NO acutely and selectively lowers the increased PP. Thus, during SHR aging, a negative feedback may be observed between NO bioactivity and PP through changes in arterial structure and function. Whether this alteration contributes to the development of systolic hypertension in old populations remains to be determined. Key Words: rats, inbred SHR Ⅲ arteries Ⅲ endothelium Ⅲ nitric oxide F or many years, studies of spontaneous hypertension in rats focused on the presence of sympathetic hyperactivity and the mechanisms by which this alteration contributes to changing the mean blood pressure (MBP) and the structure and function of arterioles. 1,2 Subsequently, the role of the vascular endothelium was principally deduced from the investigation of NO-norepinephrine (NE) interactions. 3 Nowadays, hypertension is mainly considered as a cardiovascular risk factor, leading to more attention being focused on the structure and function of hypertensive large arteries, which greatly influence the development of complications in hypertensive vascular disease. 4 It has been widely reported that the conduit arteries of spontaneously hypertensive rats (SHR) are stiffer than those of the corresponding normotensive control rats. 4,5 In addition to blood pressure level, it seems likely that intrinsic modifications of the arterial wall might contribute to the increased stiffness. 4 Because stiffness is influenced by arterial structure and function, changes in vasomotor tone, possibly of endothelial origin, might promote the alterations of the mechanical properties of the SHR conduit arteries.The purpo...

Progression of Coronary Artery Calcification and Thoracic Aorta Calcification in Kidney Transplant Recipients

“…It was also observed that NO may regulate arterial distensibility, and thus possibly pulse pressure (51). On the other hand, the elevation of pulse pressure may also exert a negative feedback on the endothelium (52). Overall, these results are in line with our findings and 16 suggest that a high pulse pressure may be a risk factor for AoC progression.…”

Relaxin Therapy Reverses Large Artery Remodeling and Improves Arterial Compliance in Senescent Spontaneously Hypertensive Rats

“…High blood pressure exacerbates the situation by forcing the artery to work in a less compliant range. 32,34,35 We found that, unlike the curly shaped elastin fibers in aortas from aged WKY rats, elastin fibers in the aorta of SHRs were straight and remained unchanged after relaxin therapy. Relaxin therapy significantly reduced collagen content, estimated either as total content per centimeter segment or percentage of dry weight but without change in elastin level, resulting in a significant increase in the elastin:collagen ratio and arterial compliance.…”

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“…Attenuation of endothelium-dependent vasodilation has been observed in elderly subjects and animal models. 48,49 Several possible mechanisms by which advancing age impairs endothelial function are postulated (Figure 2). An imbalance between NO and ROS, so-called 'oxidative stress,' should be a key regulator of age-induced endothelial dysfunction.…”